Vaccine reactogenicity, defined as local and systemic reactions, is a leading factor for COVID-19 vaccine hesitancy in adults1-4. As the perceived risk of COVID-19 decreases, individuals may become less permissive towards vaccine-associated adverse reactions.Figure 1.Study DesignFigure 2.Local and systemic reactogenicity events after Novavax or Pfizer vaccines within 1, 2, and 6 days This double-blinded RCT compared two 2023-2024 (XBB.1.5) vaccines Novavax (NVX), a protein-based vaccine, and Pfizer-BioNTech (mRNA) over a 24-week period between Nov 2023 and Aug 2024 (Fig 1). Solicited reactogenicity symptoms (systemic and local), were evaluated using a post-vaccination questionnaire at 3-time intervals (1-, 2-, and 6-days post-vaccination). Reactogenicity was assessed for occurrence and maximum intensity (according to FDA toxicity grade). Tests for linear trend were performed.Figure 3.Summary of solicited systemic reactogenicity events after Novavax or Pfizer vaccines within 1 and 2 days post-vaccination 901 participants [mean age (SD): 40.5 (15.95); 55% female; White (91%); Hispanic (11%)] completed at least one of the questionnaires (NVX n=448; mRNA n=453); all previously received ≥2 doses of mRNA vaccines prior to enrollment with 89% reported receipt of ≥3 COVID-19 vaccinations and 60% reported a prior SARS-CoV-2 infection. In review of the solicited systemic reactogenicity during the first day post-vaccination, 62.1% of NVX recipients reported experiencing any event versus 75.8% of mRNA recipients (p< 0.05) (Fig 2). On average, NVX recipients experienced 1.4 symptoms versus 2.2 in mRNA recipients (Fig 3). 15.7% of NVX recipients experienced at least one symptom of Grade 2 or higher versus 33.6% of mRNA recipients. NVX recipients had much fewer grade 2 or 3 reactogenicity events than mRNA. An absolute difference of 11.7% fewer NVX versus mRNA recipients reported solicited local reactogenicity events. The occurrence and severity of the solicited reactogenic events were transient with no difference reported at 6 days post-vaccination (Fig 2). The lower frequency and intensity of COVID-19 reactogenicity symptoms observed in this trial suggests use of the 2023/2024 adjuvanted NVX vaccine as an immunization option with lower reactogenicity. These findings may provide insight for policymakers and clinicians regarding reactogenicity that may influence patient behavior and impact choice of COVID-19 vaccination. Sarang K. Yoon, DO, MOH, Novavax: Grant/Research Support Andrew Phillips, MD, MOH, Novavax: Grant/Research Support German L. Ellsworth, MD, MPH, MOH, Novavax: Grant/Research Support Sarah W. Ball, MPH, ScD, Centers for Disease Control and Prevention, Contract #200-2019-F-06819: Grant/Research Support|Centers for Disease Control and Prevention, Contract #75D30121D12779: Grant/Research Support|Novavax: Grant/Research Support Elizabeth Rowley, DrPH, Centers for Disease Control and Prevention: Grant/Research Support|Novavax: Payments made to Westat, Inc. (employer)|University of Utah: Funded under contract with the University of Utah with prime funding and drug provided by Novavax Steph Battan-Wraith, PhD, Novavax, Inc.: Grant/Research Support Rebecca Fink, MPH, Novavax, Inc.: Grant/Research Support Adam Yates, PhD, Beehive Study: Grant/Research Support|Centers for Disease Control and Prevention, Contract #200-2019-F-06819: Grant/Research Support Seth Toback, M.D., Novavax, Inc.: employee|Novavax, Inc.: Stocks/Bonds (Public Company) Lisa M. Dunkle, MD, Novavax, Inc.: contractor for Novavax|Novavax, Inc.: Stocks/Bonds (Public Company) Matthew D. Rousculp, PhD, Novavax, Inc.: employee|Novavax, Inc.: employee|Novavax, Inc.: Stocks/Bonds (Private Company)|Novavax, Inc.: Stocks/Bonds (Private Company)

NVX-CoV2373 is a nanoparticle, protein-based COVID-19 vaccine. Individuals who are immunocompromised (IIC) are at high risk for infection and severe disease; however, real-world NVX-CoV2373 impact data in IIC are limited. The objective of this study was to assess whether NVX-CoV2373 reduced the risk of SARS-CoV-2 infection and severe disease in IIC, compared to non-immunocompromised (non-IC) individuals. South Korean IIC aged ≥12 years who received a primary series, third dose, or fourth dose of NVX-CoV2373 were identified in The Korea Disease Control and Prevention Agency-COVID-19-National Health Insurance Service (K-COV-N) database. IIC were propensity score matched to non-IC individuals to minimize potential confounding. Outcomes were any and severe SARS-CoV-2 infections, collected in cumulative 30-day risk windows through 180 days post vaccination in primary series and third- and fourth-dose groups. Adjusted hazard ratios (aHRs) measured relative vaccine impact by comparing outcomes between IIC and non-IC individuals across dose groups, overall, and by immunocompromising condition. A total of 755,727 doses of NVX-CoV2373 were administered from February–December 2022, with 400,435 IIC individuals included in this analysis. Through 180 days, aHRs (95

Background Surveillance of COVID-19 vaccine effectiveness (VE) was extensive upon vaccine introduction; however, it declined after the withdrawal of pandemic status in May 2023. Continued monitoring of updated vaccine formulations is needed to ensure the maintenance of VE in the face of evolving viral strains. Objective The Booster Epidemiological Evaluation of Health, Illness and Vaccine Efficacy (BEEHIVE) study (NCT06065176), a randomized trial with a hybrid design, was developed to assess the real-world VE of the 2023-2024 Pfizer–BioNTech and Novavax COVID-19 vaccine formulations targeting the XBB.1.5 SARS-CoV-2 variant. Methods This study was designed to enroll approximately 1500 participants aged ≥18 years from the Salt Lake City, Utah, area who had previously received ≥2 doses of an authorized messenger RNA (mRNA)–based COVID-19 vaccine but had not received a dose of the 2023-2024 formulation. The study used a randomized, hybrid design comprising 2 blinded groups assigned to receive the 2023-2024 formula of either the Novavax COVID-19 vaccine or the Pfizer–BioNTech COVID-19 vaccine and a nonrandomized, observational control group of volunteers who chose not to receive a 2023-2024 vaccine dose during the study. Follow-up lasted 24 weeks and included symptom surveys and self-administered COVID-19 antigen testing, both occurring weekly. The primary aim was to compare VE (defined as prevention of symptomatic SARS-CoV-2 infection) between study-vaccinated participants and the control group. The secondary aim was to determine the relative VE of the Pfizer–BioNTech mRNA and Novavax 2023-2024 COVID-19 vaccines. Secondary objectives included assessing how the number of previous COVID-19 vaccinations impacted VE of the 2023-2024 COVID-19 vaccines; identifying predictors and associated factors for asymptomatic versus symptomatic infection and/or prolonged or severe illness; examining factors associated with post–COVID-19 conditions; and evaluating participants’ knowledge, attitudes, and practices related to COVID-19 vaccination. Participant engagement was maintained via online and text-based reminders and surveys, as well as researcher follow-up. Results Participants were recruited from November 2023 through March 2024, with 452 and 457 participants randomized to the Novavax and Pfizer–BioNTech vaccine groups, respectively, and 279 participants enrolled in the control group. SARS-CoV-2 variants from the XBB, JN.1, KP.2, and KP.3 lineages were in circulation in the United States and the Utah region during data collection. The study ended on September 9, 2024, with results expected to be published in 2026. Conclusions Data from this study will provide valuable real-world VE data for a dose of the Novavax COVID-19 vaccine or the Pfizer–BioNTech COVID-19 vaccine after an mRNA-based COVID-19 primary series. Trial Registration ClinicalTrials.gov NCT06065176; https://www.clinicaltrials.gov/study/NCT06065176 International Registered Report Identifier (IRRID) RR1-10.2196/80858

Objectives:To compare the percentage of participants that experienced any solicited reactogenicity symptom after 1 dose of the updated 2024-2025 adjuvanted protein-based Novavax (NVX; JN.1) or Pfizer-BioNTech mRNA (PFZ; KP.2) COVID-19 vaccine within 2 and 7 days post-vaccination and examine its impact on daily life. Methods:In this prospective, interventional, real-world study (SHIELD/NCT06633835), previously vaccinated healthcare workers (HCWs) and first responders (FRs) from Salt Lake City, Utah, United States, and surrounding areas self-selected to receive NVX or PFZ. At 2 and 7 days post-vaccination, participants self-reported on 11 vaccine-related reactogenicity symptoms and functional impairment using a 5-item modified Sheehan Disability Scale. Results:Five hundred eighty-eight participants completed the day 2 questionnaire (NVX, n =219; PFZ, n =369); 583 completed the day 7 questionnaire (NVX, n =217; PFZ, n =366). Two days post-vaccination, NVX recipients were less likely to report a systemic (OR =0.40; 95% CI, .21-.75) or local (OR =0.10; 95% CI, .03-.33) reactogenicity symptom and lost 50% fewer work hours (0.7 vs 1.4 hours) and 66% fewer productive hours (0.8 vs 2.4 hours) than PFZ recipients. There was little to no difference between vaccines at 7 days post-vaccination. Conclusions:Fewer reactogenicity symptoms following COVID-19 vaccination suggest use of the 2024-2025 adjuvanted protein-based NVX vaccine as an immunization option with a lower impact on daily life. These findings may inform policymakers, clinicians, and hospital systems regarding vaccine tolerability, which may influence HCW and FR behavior regarding COVID-19 vaccines.

BACKGROUND:Real-world vaccine effectiveness (VE) and relative VE (rVE) data of protein-based and mRNA COVID-19 vaccines against symptomatic SARS-CoV-2 infections inform policy recommendations and reinforce public confidence. The study aim was to assess the safety and VE of the 2023-2024 protein-based and mRNA COVID-19 vaccines (XBB.1.5) in a real-world setting. METHODS:The single-site, pragmatic BEEHIVE clinical trial was conducted among participants aged ≥18 years from the Salt Lake City, Utah, area, who had previously received ≥2 mRNA COVID-19 vaccines, from November 17, 2023, through September 9, 2024. Randomized participants received a protein-based or mRNA COVID-19 vaccine in a double-blind manner. An unblinded, nonrandomized comparator control group that did not receive a study vaccine was also enrolled. The primary aim measured VE between the randomized and comparator groups. The secondary aim was to measure rVE between the 2 vaccine platforms. In the modified intention-to-treat (mITT) analysis, VE and rVE were estimated using a proportional-hazards model for symptomatic infections confirmed by weekly self-administered rapid antigen tests (RATs) over 24 weeks, adjusted for covariates. Reactogenicity and treatment-emergent adverse events (TEAEs) were recorded. RESULTS:Randomized cohorts (N = 909; protein-based, n = 452; mRNA, n = 457) were largely well-balanced with some differences in baseline covariates versus the comparator group (n = 279), mostly age-related. The mITT population had 142 RAT-confirmed symptomatic SARS-CoV-2 cases with an adjusted VE of 43.6% (95% CI, 18.3-61.0); rVE (protein-based vs mRNA) was -26.7% (90% CI, -78.6% to 10.1%) and did not reach statistical significance. Safety and reactogenicity were comparable to previously reported findings, with no serious study vaccine-related TEAEs, myocarditis/pericarditis, hospitalization, or death. CONCLUSIONS:This is one of the earliest real-world trials evaluating the VE of the 2023-2024 COVID-19 vaccines (XBB.1.5). These results suggest that both protein-based and mRNA vaccines are well-tolerated and significantly reduce the risk of symptomatic SARS-CoV-2 infections.

Background/Objectives: The Novavax COVID-19 vaccine (Nuvaxovid™) was authorized in France in December 2021, assisting in ending the global pandemic and providing an alternative to other COVID-19 vaccines. Understanding Nuvaxovid recipients’ profile is essential for guiding vaccination decision-making and maintaining protection amid declining COVID-19 vaccination rates. Methods: This retrospective, observational study characterizes the evolution of French Nuvaxovid recipients’ demographic and clinical characteristics using the Système National des Données de Santé (SNDS) database. Five study seasons (spring 2022, autumn 2022, spring 2023, autumn 2023, spring 2024) were defined based on French vaccination guidelines and Nuvaxovid authorization dates. T-test and Chi-square tests were used to compare between consecutive seasons and subgroups. Results: Nuvaxovid administration was reported in 9805 recipients during spring 2022, 5601 during autumn 2022, 531 during spring 2023, 980 during autumn 2023, and 909 during spring 2024. Statistically significant increases in the proportions of high-risk (spring 2022: 35.4%, spring 2024: 90.5%) and ≥65-year-old (spring 2022: 19.9%, spring 2024: 84.4%) Nuvaxovid recipients were observed, p < 0.05. Comorbidities, notably cardiovascular disease, became progressively more prevalent (spring 2022: 7.1%, spring 2024: 33.7%, p < 0.05). Nuvaxovid was used nationwide, with a higher proportion of recipients in the southeast, a region typically exhibiting lower vaccine coverage. Most Nuvaxovid recipients increasingly received a heterologous regimen (autumn 2022: 91%, spring 2024: 98.6%, p < 0.05), with Nuvaxovid as the ≥4th dose (55–97.2%, p < 0.05). Meanwhile, higher proportions of <65-year-old and not-at-risk recipients received Nuvaxovid as primary series (autumn 2022: 46.9% <65-year-old vs. 5.6% ≥65-year-old, 53.9% not at risk vs. 11.9% at risk, p < 0.05). Conclusions: The use of Nuvaxovid evolved in accordance with changing clinical recommendations, and mix-and-match vaccination strategies and heterologous vaccination patterns suggest that it served as an important protein-based alternative for those switching from other COVID-19 vaccines. Nuvaxovid offers a valuable choice, so that the most vulnerable continue to be vaccinated.

BACKGROUND AND AIMS:Adolescents can have severe/chronic outcomes from COVID-19. Real-world data on relative vaccine effectiveness between mRNA- and protein-based vaccines are limited, and more data are needed on disease outcomes in this age group. METHODS:The K-COV-N database, COVID-19 vaccine registry and health insurance claims were retrospectively reviewed to identify adolescents (12- to 18-year-olds) in South Korea who received a homologous primary series of NVX-CoV2373 or BNT162b2 and a heterologous or homologous third vaccine dose. Vaccine recipients were propensity score matched to reduce confounding baseline factors. Adjusted hazard ratios (aHRs) for any medically attended COVID-19 postvaccination (starting 14 days after primary series and 7 days after a third dose) were calculated to assess relative vaccine effectiveness every 30 days through a 180-day risk window. RESULTS:From February to December 2022, 3174 and 6253 doses of NVX-CoV2373 and BNT162b2, respectively, were administered to South Korean adolescents. Individuals who received NVX-CoV2373 tended to be older, have a disability, and/or have a prior SARS-CoV-2 infection. Propensity score matching resulted in 107 individuals in each primary series group and 701 and 1417 individuals in the NVX-CoV2373 and BNT162b2 third-dose groups, respectively. The aHR (95% CI) for NVX-CoV2373 compared with BNT162b2 for medically attended COVID-19 in the 180-day risk window was 0.57 (0.31-1.05) for the primary series and 0.68 (0.54-0.84) for the third dose. CONCLUSIONS:These results suggest that NVX-CoV2373 may provide more robust protection against medically attended COVID-19 as a third dose, compared with BNT162b2. While the aHR for the primary series also indicated lower risk with NVX-CoV2373, this difference was not statistically significant.

NVX-CoV2373 is a nanoparticle, protein-based COVID-19 vaccine. Individuals who are immunocompromised (IIC) are at high risk for infection and severe disease; however, real-world NVX-CoV2373 effectiveness data in IIC are limited. South Korean IIC aged ≥12 years who received a primary series, third dose, or fourth dose of NVX-CoV2373 were identified in The Korea Disease Control and Prevention Agency-COVID-19-National Health Insurance Service (K-COV-N) database. IIC were propensity score matched to non-immunocompromised (non-IC) individuals to minimize potential confounding. Outcomes were any and severe SARS-CoV-2 infections, collected in cumulative 30-day risk windows through 180 days post vaccination in primary series and third and fourth dose groups. Adjusted hazard ratios (aHRs) measured relative vaccine effectiveness by comparing IIC and non-IC individuals across dose groups, overall, and by immunocompromising condition. A total of 755,727 doses of NVX-CoV2373 were administered to IIC February– December 2022, with 403,259 IIC included in this analysis. Through 180 days, aHRs (95% CI) for any SARS-CoV-2 infection were 1.10 (1.06–1.14), 1.05 (1.01–1.09), and 1.03 (1.02–1.05) for the primary series, third-dose, and fourth-dose groups; severe infection: 0.76 (0.52–1.12), 0.90 (0.53–1.51), and 1.11 (0.87–1.41), respectively. Risk estimates for any infection were relatively consistent across risk windows and among most immunocompromising conditions. NVX-CoV2373 provided similar protection among IIC and non-IC individuals regardless of dose administered and IC condition.

Abstract Background Post-marketing assessments of vaccine effectiveness (VE) are critical to informing health policy, understanding real-world vaccine performance, and ensuring confidence in vaccination efforts, though imperfect comparator groups can limit the accuracy of VE assessments. The self-controlled risk interval (SCRI) design, a case-only analytic method historically used in safety studies, controls for time-invariant confounding using within-person comparisons and has recently been used to assess VE. This targeted review identifies and characterizes SCRI’s growing role in VE research.Table 1:Vaccine Effectiveness Studies that Used the Self-Controlled Risk Interval Design Methods Targeted database searches were conducted in Medline, Embase®, Embase Preprints, and BIOSIS Previews®, and the preprint servers: medRxiv, preprints with The Lancet, and Research Square. Key terms (and related variations) included: vaccine effectiveness, COVID-19 vaccines, and self-controlled risk interval. Results Two VE studies that used the SCRI design were identified (Table 1). Both were retrospective database studies (one using electronic health records and the other insurance claims data), evaluated SARS-CoV-2 infection, and used similar post-vaccination control windows, but featured different post-vaccination risk windows and were conducted among notably different populations. An additional 10 identified studies included post-vaccination person-time in the comparison group but did not make within-person comparisons to address important potential confounding, acknowledging that post-vaccination benefits are not appreciated immediately. These studies varied in the study populations, outcomes assessed, comparison group composition, and analytic methods. Conclusion Use of SCRI for VE estimation has been limited; however, the increasing inclusion of post-vaccination control arm person-time in other COVID-19 VE studies merits the broadening of its application. The results of this review suggest that, in the context of COVID-19, SCRI VE evaluation is a promising tool where there are no suitable comparison groups, increasingly complex individual backgrounds (e.g., infection history, number and timing of doses, or heterologous vaccination), or insufficient information for confounding control. Disclosures Jonathan Fix, PhD, Novavax, Inc.: employee|Novavax, Inc.: Stocks/Bonds (Public Company) Anthony M. Marchese, PhD, Novavax Inc: Employee|Novavax Inc: Stocks/Bonds (Public Company) Hadi Beyhaghi, MD, PhD, Novavax, Inc.: employee|Novavax, Inc.: Stocks/Bonds (Public Company) Matthew D. Rousculp, PhD, Novavax, Inc.: employee|Novavax, Inc.: Stocks/Bonds (Public Company)

Reactogenicity, the occurrence of vaccine side effects, can impact vaccine acceptance. There is limited data comparing the reactogenicity of COVID-19 vaccines to other routinely used vaccines, such as the meningococcal conjugate vaccine (MenACWY). In a trial of UK adults, participants received a third COVID-19 vaccine dose (NVX-CoV2373, BNT162b2, or mRNA1273) alongside MenACWY as an active control. Compared to MenACWY, we found that mRNA vaccines, particularly mRNA1273, showed the greatest relative increase in side effects, while protein-based NVX-CoV2373 generally elicited similar reactogenicity to MenACWY. These findings suggest that platform type can influence vaccine reactogenicity, and further research is needed to compare COVID-19 vaccines with other routinely administered vaccines.

Vaccination has dramatically reduced the global burden of pediatric vaccine-preventable diseases, yet a decline in immunization rates in recent years has led to the re-emergence of diseases once nearing eradication, such as measles and pertussis. This trend is of particular concern for children with chronic conditions or those who are immunocompromised, as they face elevated risks of severe illness and complications.Parental vaccine hesitancy (PVH) plays a central role in this decline and is a multifactorial phenomenon shaped by demographic and socioeconomic factors, the child's health condition, parental attitudes and personal experiences, perceived disease risk and trust in the government and healthcare system.This targeted literature review demonstrates a consistent association between prior experiences of vaccine reactogenicity among parents or caregivers and subsequent hesitancy to vaccinate their children. Even mild or anticipated adverse events following immunization (AEFIs) can trigger emotional aversion or anxiety, lead to overestimation of the likelihood and severity of future reactions, erode trust in the healthcare system and vaccine safety information, and open susceptibility to anti-vaccine rhetoric, particularly when experienced by parents or their children. These experiences often outweigh clinical evidence in shaping vaccine decisions and contribute to long-term hesitancy.Addressing PVH requires a multifaceted approach. Healthcare providers must engage in empathetic, transparent communication, offering clear information about expected side effects and differences in vaccine platforms. Where feasible, offering less reactogenic vaccine options may help mitigate concerns. Additionally, proactively optimizing vaccine formulations for low reactogenicity in early development could reduce downstream hesitancy and improve public confidence. By acknowledging the emotional and experiential dimensions of PVH, public health strategies can better support informed parental decision-making and improve vaccine uptake in vulnerable pediatric populations.

OBJECTIVES:In February 2022, NVX-CoV2373 became available in South Korea; real-world effectiveness of multiple doses compared with mRNA-based vaccines has not been thoroughly evaluated. METHODS:This retrospective study identified NVX-CoV2373 and BNT162b2 recipients aged ≥12 years from the K-COV-N database. Vaccine groups were propensity score-matched based on demographic characteristics, Seoul capital area residence, income level, comorbidity/disability, prior SARS-CoV-2 infection, and prior vaccination dose/timing. Outcomes were any and severe (intensive-care-unit admission or death within 8 weeks of infection) laboratory-confirmed SARS-CoV-2 infection assessed from 7 days after the third and fourth dose. Adjusted hazard ratios (aHRs) from matched groups measured vaccine effectiveness up to a 180-day risk window. RESULTS:From February to December 2022, 923,833 NVX-CoV2373 and 1,286,604 BNT162b2 doses were administered. The 180-day risk-window aHRs (95% CI) for NVX-CoV2373 compared with BNT162b2 for any SARS-CoV-2 infection were 0.78 (0.76-0.79) post third dose and 0.86 (0.86-0.87) post fourth dose. The 180-day aHRs (95% CI) for severe infection were 0.73 (0.53-1.00) after the third dose and 1.21 (1.03-1.42) after the fourth dose. CONCLUSIONS:NVX-CoV2373 demonstrated favorable and similar effectiveness against any and severe SARS-CoV-2 infection, respectively, compared with BNT162b2, with evidence of enhanced NVX-CoV2373 durability.

Background/Objectives: Precautionary health behaviours (PHBs), such as hand-washing or self-isolation, are non-pharmaceutical interventions used to reduce SARS-CoV-2 transmission. We investigated the potential confounding by PHBs of COVID-19 vaccine effectiveness (VE) estimates in a subset of study participants enrolled in id.DRIVE. Methods: The id.DRIVE COVID-19 VE study (formerly COVIDRIVE) is a European multicentre test-negative case–control study estimating COVID-19 VE against hospitalisation due to laboratory-confirmed SARS-CoV-2 in patients with severe acute respiratory infection. All adults (≥18 y) prospectively enrolled between 16 November 2021 and 16 August 2023 at three sites were invited to complete a PHB survey capturing indicators of PHBs in the 3 months preceding admission. Fisher’s exact test with Bonferroni-adjusted threshold was used to measure the level of association between PHB indicators and both COVID-19 vaccine status and SARS-CoV-2 test result. VE estimates were generated with and without adjustment for PHBs. Results: PHBs were modified over time, with higher precautionary attitudes in the first COVID-19 vaccine booster season (2021–2022) compared to the second one (2022–2023). For the first booster season, PHBs were positively associated with exposures (vaccination status) and outcomes (case or control status). Adjusting for PHBs led to a 6 to 9 percentage-point increase in VE estimates. Conversely, no confounding by PHBs was observed in the second booster season. Conclusions: PHBs should be considered a possible confounder of COVID-19 VE studies. Further research is needed to define when PHBs should be integrated into VE models, as the level of confounding may differ according to the study population and the epidemiological context.

To estimate the relative effectiveness of NVX-CoV2373 versus BNT162b2 (Pfizer-BioNTech) in preventing SARSCoV-2 infection and severe COVID-19 disease during the Omicron variant dominance in South Korea, we conducted a retrospective cohort-study among >= 12-year-olds using the K-COV-N database, which links COVID-19 vaccine registry data with health insurance claims data. The Cox proportional-hazards model and inverse probability of treatment weighting were employed to calculate adjusted hazard ratios (aHRs). Among homologous primary-series NVX-CoV2373 versus BNT162b2 recipients at Day 180 post-vaccination, the aHR was 0.90 (95% CI: 0.87-0.93) for all laboratory-confirmed and 0.65 (95% CI: 0.48-0.88) for severe infections. Among homologous 1st-booster recipients, it was 1.15 (95% CI: 1.01-1.30) for all laboratory-confirmed and 0.39 (95% CI: 0.20-0.75) for severe infections. At 180-days post-immunization, we observed homologous, NVX-CoV2373 primary-series added and 1st booster offered comparable protection against SARS-CoV-2 infection versus BNT162b2.

Individuals who are immunocompromised (IIC) may have impaired infection prevention/resolution, potentially causing increased disease severity, complications, and healthcare-system strain. Exclusion of IIC from COVID-19 vaccine trials and limited real-world Novavax COVID-19 vaccine assessments have resulted in a data gap. This article provides a review of literature on IIC who received the Novavax COVID-19 vaccine. A targeted literature search of BIOSIS Previews®, Embase®, Embase Preprints, MEDLINE®, and publicly available content was performed to identify published clinical data assessing efficacy, immunogenicity, and safety of the Novavax COVID-19 vaccine in IIC, with predefined terms for immune-modifying diseases/conditions and medications. Identified publications were screened to ensure they described study data from IIC who received the Novavax COVID-19 vaccine. The search (through October 2024) identified 137 reports indicating use of the Novavax COVID-19 vaccine in IIC. Screening resulted in 10 publications for review; exclusionary reasons included a lack of vaccine-specific data (i.e., limited [<0.2% or n < 3] vaccine recipients, pooled/aggregated cohorts) and/or IIC population. Conditions described include HIV, multiple sclerosis, inflammatory rheumatic diseases, transplant recipients, and hematologic malignancies. Overall, the Novavax COVID-19 vaccine was immunogenic and had a tolerable safety profile across diverse populations of IIC; some outcomes varied based on condition, disease, and/or concomitant medication(s). Limited efficacy data indicates that the Novavax COVID-19 vaccine may help protect IIC against symptomatic/severe COVID-19; however, additional studies with larger sample sizes are needed. Future research should include disease-specific populations to assess how individual characteristics (e.g., disease state, concomitant medications, prior COVID-19 vaccination) impact vaccine response.

BackgroundDespite strong evidence supporting COVID-19 vaccine efficacy and safety, a proportion of the population remains hesitant to receive immunization. Discrete choice experiments (DCEs) can help assess preferences and decision-making drivers. ObjectiveWe aim to (1) elicit preferences for COVID-19 vaccines in Canada, Germany, the United Kingdom, and the United States; (2) understand which vaccine attributes people there value; and (3) gain insight into the choices that different population subgroups make regarding COVID-19 vaccines. MethodsParticipants in the 2019nCoV-408 study were aged ≥18 years; self-reported antivaccinationists were excluded. A DCE with a series of 2 hypothetical vaccine options was embedded into a survey to determine participant treatment preferences (primary objective). Survey questions covered vaccine preference, previous COVID-19 experiences, and demographics, which were summarized using descriptive statistics to understand the study participants’ backgrounds. In the DCE, participants were provided choice pairs: 1 set with and 1 without an “opt-out” option. Each participant viewed 11 unique vaccine profiles. Vaccine attributes consisted of type (messenger RNA or protein), level of protection against any or severe COVID-19, risk of side effects (common and serious), and potential coadministration of COVID-19 and influenza vaccines. Attribute level selections were included for protection and safety (degree of effectiveness and side effect risk, respectively). Participants were stratified by vaccination status (unvaccinated, or partially or fully vaccinated) and disease risk group (high-risk or non–high-risk). A conditional logit model was used to analyze DCE data to estimate preferences of vaccine attributes, with the percentage relative importance calculated to allow for its ranking. Each model was run twice to account for sets with and without the opt-out options. ResultsThe mean age of participants (N=2000) was 48 (SD 18.8) years, and 51.25% (1025/2000) were male. The DCE revealed that the most important COVID-19 vaccine attributes were protection against severe COVID-19 or any severity of COVID-19 and common side effects. Protection against severe COVID-19 was the most important attribute for fully vaccinated participants, which significantly differed from the unvaccinated or partially vaccinated subgroup (relative importance 34.8% vs 30.6%; P=.049). Avoiding serious vaccine side effects was a significantly higher priority for the unvaccinated or partially versus fully vaccinated subgroup (relative importance 10.7% vs 8.2%; P=.044). Attributes with significant differences in the relative importance between the high-risk versus non–high-risk subgroups were protection against severe COVID-19 (38.2% vs 31.5%; P<.000), avoiding common vaccine side effects (12% vs 20.5%; P<.000), and avoiding serious vaccine side effects (9.7% vs 7.5%; P=.002). ConclusionsThis DCE identified COVID-19 vaccine attributes, such as protection against severe COVID-19, that may influence preference and drive choice and can inform vaccine strategies. The high ranking of common and serious vaccine side effects suggests that, when the efficacy of 2 vaccines is comparable, safety is a key decision-making factor.

Policymakers in the United States (US) recommend coronavirus disease 2019 (COVID-19) vaccination with a monovalent 2023-2024 vaccine formulation based on the Omicron XBB.1.5 variant. We estimated the potential US population-level health and economic impacts of increased COVID-19 vaccine coverage that might be expected with the availability of a protein-based vaccine with simpler storage requirements in addition to messenger ribonucleic acid (mRNA) vaccines. A Markov model was developed to estimate 1-year COVID-19-related costs, cases, hospitalizations, and deaths with and without the availability of a protein-based vaccine option. The model population was stratified by age and risk status. Model inputs were sourced from published literature or derived from publicly available data. Our model estimated that a five-percentage-point increase in coverage due to the availability of a protein-based vaccine option would prevent over 500,000 cases, 66,000 hospitalizations, and 3000 COVID-19-related deaths. These clinical outcomes translated to 42,000 quality-adjusted life years (QALYs) gained and an incremental cost-effectiveness ratio of USD 16,141/QALY from a third-party payer perspective. In sensitivity analyses, outcomes were most sensitive to COVID-19 incidence and severity across age groups. The availability of a protein-based vaccine option in the US could reduce hospitalizations and deaths and is predicted to be cost-effective.

This phase 3 observer-blind, randomized, controlled study was conducted in adults ≥18 years of age to assess the safety and immunogenicity of NVX-CoV2373 as a heterologous booster compared to BBIBP-CorV when utilized as a homologous booster. Approximately 1000 participants were randomly assigned in a 1:1 ratio to receive a single dose of NVX-CoV2373 or BBIBP-CorV after prior vaccination with 2 or 3 doses of BBIBP-CorV. Solicited adverse events (AEs) were collected for 7 days after vaccination. Unsolicited AEs were collected for 28 days following the booster dose and serious adverse and adverse events of special interest (AESI) were collected throughout the study. Anti-spike IgG and neutralizing antibodies against SARS-CoV-2 were measured at baseline, day 14, day 28, and day 180. The study achieved its primary non-inferiority endpoint and also demonstrated statistically higher neutralization responses when NVX-CoV2373 was utilized as a heterologous booster compared with BBIBP-CorV as a homologous booster. Both vaccines had an acceptably low reactogenicity profile, and no new safety concerns were found. Heterologous boosting with NVX-CoV2373 was a highly immunogenic and safe vaccine regimen in those previously vaccinated with BBIBP-CorV.

Participants in studies investigating COVID-19 vaccines commonly report reactogenicity events, and concerns about side effects may lead to a reluctance to receive updated COVID-19 vaccinations. A real-world, post hoc analysis, observational 2019nCoV-406 study was conducted to examine reactogenicity within the first 2 days after vaccination with either a protein-based vaccine (NVX-CoV2373) or an mRNA vaccine (BNT162b2 or mRNA-1273) in individuals who previously completed a primary series. Propensity score adjustments were conducted to address potential confounding. The analysis included 1130 participants who received a booster dose of NVX-CoV2373 (n = 303) or an mRNA vaccine (n = 827) during the study period. Within the first 2 days after vaccination, solicited systemic reactogenicity events (adjusted) were reported in 60.5% of participants who received NVX-CoV2373 compared with 84.3% of participants who received an mRNA vaccine; moreover, 33.9% and 61.4%, respectively, reported ≥3 systemic reactogenicity symptoms. The adjusted mean (95% CI) number of systemic symptoms was 1.8 (1.6–2.0) and 3.2 (3.0–3.4), respectively. Local reactogenicity events (adjusted) were reported in 73.4% and 91.7% of participants who received NVX-CoV2373 and mRNA vaccines, respectively; the adjusted mean (95% CI) number of local symptoms was 1.5 (1.33–1.61) and 2.4 (2.31–2.52), respectively. These results support the use of adjuvanted, protein-based NVX-CoV2373 as an immunization option with lower reactogenicity than mRNAs.

As SARS-CoV-2 variants continue to emerge, vaccination remains a critical tool to reduce the COVID-19 burden. Vaccine reactogenicity and the impact on work productivity/daily activities are recognized as contributing factors to vaccine hesitancy. To encourage continued COVID-19 vaccination, a more complete understanding of the differences in reactogenicity and impairment due to vaccine-related side effects across currently available vaccines is necessary. The 2019nCoV-406 study (n = 1367) was a prospective observational study of reactogenicity and associated impairments in adults in the United States and Canada who received an approved/authorized COVID-19 vaccine. Compared with recipients of mRNA COVID-19 booster vaccines, a smaller percentage of NVX-CoV2373 booster recipients reported local and systemic reactogenicity. This study’s primary endpoint (percentage of participants with ≥50% overall work impairment on ≥1 of the 6 days post-vaccination period) did not show significant differences. However, the data suggest that NVX-CoV2373 booster recipients trended toward being less impaired overall than recipients of an mRNA booster; further research is needed to confirm this observed trend. The results of this real-world study suggest that NVX-CoV2373 may be a beneficial vaccine option with limited impact on non-work activities, in part due to the few reactogenicity events after vaccination.